The invention relates to a device and method for moving an ion source in a magnetic field by means of the Lorentz force.
Electron impact ionization is a well-established and frequently used standard method for generating ions in mass spectrometers. Perhaps the most widely used electron emission device basically consists of a metal filament. An electrical current flowing through this filament makes it glow. By applying an electrical voltage, the electrons which leave the filament due to the thermionic emission are xe2x80x9cextractedxe2x80x9d and accelerated. If one of these electrons now collides with a neutral molecule with an ionization energy lower than the kinetic energy of the electron, then a positive ion is formed from this molecule (electron impact ionization). Thermal electrons, on the other hand, can produce negative ions from neutral molecules by a process of electron attachment or electron capture. During the formation of a positive ion, collisions with electrons which have a significantly higher kinetic energy than the ionization energy of the molecule leads to an increase of the internal energy of the molecular ion. This process usually ends with a fragmentation of the molecular ion. Therefore, fragment ion signals are also produced if electron impact ionization takes place at energies which are usually applied in mass spectrometry, typically 70 eV. This situation is often desirable since fragment-ion spectra provide valuable information about the structure of the molecule.
An additional fragmentation (dissociation) of ions is generally used in analytical mass spectrometry for determination of ionic structures since the generation of fragment ions (daughter ions) is directly related to the structure and chemical bonds of the ion to be fragmented. Consequently, the fragment spectrum is a characteristics of the parent ion (precursor) and represents a sort of xe2x80x98fingerprintxe2x80x99. Perhaps the most well known standard method of ion fragmentation in mass spectrometry relies on the acceleration of ions to be fragmented and their collision with the atoms or molecules of a collision-gas (collision-induced dissociation, collision-induced decomposition or CID). Collisions increase the internal energy of the ions, particularly the oscillation energy, enough to break weak chemical bonds. An overview of CID is provided in: Jennings, K. R. xe2x80x9cThe Changing Impact of the Collision-Induced Decomposition of Ions on Mass Spectrometryxe2x80x9d Int. J. Mass Spectrom. 2000, 200, 479-493.
Another fragmentation method which is being increasingly used is the infrared multiphoton dissociation (IRMPD). In this case, an ion is excited by several, sequentially absorbed photons from an infrared laser (such as a CO2 laser). Subsequently, dissociation products are observed which are similar to those produced by CID. For mass spectrometric methods which require very low pressures (ultra-high vacuum), IRMPD is a popular alternative since there is no need for collision gas to be introduced into the mass spectrometer for the ion fragmentation. By using CID or IRMPD, peptide or protein ions produce so-called b and y fragments, which are produced as a result of the cleavage of the bond between the peptide nitrogen atom and the neighboring carboxyl carbon atom. In order to use the infrared multiphoton dissociation, the IR laser beam and the ions must be brought to the same place. The interaction between the ions and the laser beam can best be achieved in an ion trap. An ion trap means here a Paul trap (RF ion trap or quadrupole trap), a Penning trap (ion-cyclotron resonance or ICR trap) or a linear RF multipole trap. The latter consists of a multipole ion guide device with two end electrodes (such as apertured end plates) to which a relatively low DC voltage is applied. If ions are to be stored in the trap, the voltages of the two apertured end plates are of the same polarity as the charge on the ions. The stored ions are extracted by reversing the polarity of the voltage at one of these end plates. For performing infrared multiphoton dissociation experiments of ions in one of these traps, an infrared laser beam is introduced, usually along the axis through the aperture of one of the terminal plates (terminal diaphragms in the case of a linear multipole trap or trapping plates in the case of an FT ICR (Fourier transform ion-cyclotron resonance) trap or end caps in the case of a Paul trap). The following represents some of the literature which deals with IRMPD applications. FT ICR mass spectrometry: Shi, S. D. H., Hendrickson, C. L., Marshall, A. G., Siegel, M. M., Kong, F. and Carter, G. T. xe2x80x9cStructural Validation of Saccharomicins by High Resolution and High Mass Accuracy Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Infrared Multiphoton Dissociation Tandem Mass Spectrometryxe2x80x9d J. Am. Soc. Mass Spectrom. 1999, 10, 1285-1290. Paul traps: Colorado, A., Shen, J. X., Vartanian, V. H. and Brodbelt, J. xe2x80x9cUse of Infrared Multiphoton Photodissociation with SWIFT for Electrospray Ionization and Laser Desorption Applications in a Quadrupole Ion Trap Mass Spectrometerxe2x80x9d Anal, Chem. 1996, 68, 4033-4043. Linear RF multipole traps: Hofstadler, S. A., Sannes-Lowery, K. A. and Griffey, R. A. xe2x80x9cInfrared Multiphoton Dissociation in an External Ion Reservoirxe2x80x9d Anal. Chem. 2000, 71, 2067-2070.
For many applications with stored ions Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS or FTMS for short) is popular because of its very high mass accuracy and mass resolution. As a consequence, all possible fragmentation methods are used in FTMS. A review of FT ICR mass spectrometry is provided in: Marshall, A. G., Hendrickson, C. L. and Jackson, G. S. xe2x80x9cFourier Transform Ion Cyclotron Mass Spectrometry: A Primerxe2x80x9d Mass Spectrom. Rev. 1998, 17, 1-35.
Until now, fragmentation methods have been described which are either based on collisions between the molecular ions and the collision gas particles or on the interaction of ions with photons. A new fragmentation method introduced few years ago in the FT-ICR mass spectrometry relies on the interaction between electrons and ions. During this process multiply-charged positive ions capture low-energy electrons and produce cationic dissociation products. This process is referred to as electron capture dissociation or ECD. Multiply-charged positive ions can be produced by a method such as electrospray ionization. Electron capture dissociation of peptide or protein ions mostly produces c or z type fragment ions. These c or z fragment ions, which usually do not appear during CID or IRMPD processes, are formed as a result of the cleavage of the bond between the amino nitrogen atom participating in the peptide bond and the neighboring carbon atom from which the amino group originates. The c and z fragments produced by electron capture dissociation provide information which is complementary to that provided by IRMPD and CID, and consequently lead to a more complete mass-spectrometric sequence determination of polypeptides and proteins. The following literature is recommended for reading about the basis and applications of the ECD method: McLafferty, F. W., Horn, D. M., Breuker, K., Ge, Y., Lewis, M. A., Cerda, B., Zubarev, R. A. and Carpenter, B. K. xe2x80x9cElectron Capture Dissociation of Gaseous Multiply Charged Ions by Fourier Transform Ion Cyclotron Resonancexe2x80x9d J. Am. Soc. Mass Spectrom. 2001, 12, 245-149 and Zubarev, R. A., Horn, D. M., Fridriksson, E. K., Kelleher, N. L., Kruger, N. A., Lewis, M. A., Carpenter, B. K. and McLafferty, F. W. xe2x80x9cElectron Capture Dissociation for Structural Characterization of Multiply Charged Protein Cationsxe2x80x9d Anal. Chem. 2000, 72, 563-573.
The efficiency of ECD primarily depends among others also on the number of electrons and their orbits in the trap. In FT ICR mass spectrometry, a filament produces electrons outside the ICR trap and axial to it. These are then guided into the trap parallel to the magnetic field. As for thermal conductivity reasons only the center of the filament heats up enough to generate electrons, the electron beam is produced within the magnetic field is like a thin thread. After the electron beam is once formed, all attempts to broaden this thin beam fail under the given energetic conditions, since movements perpendicular to the magnetic field, typically several Tesla strong, also cause a perpendicular Lorentz force which makes the electrons circle in tiny cyclotron orbits. The electron beam must therefore be generated initially with a larger diameter. Recently, large area electron emitters have been used to generate electrons for ECD experiments and as a consequence, the probability of the ion orbits overlapping with the low energy electrons is increased dramatically, which also increased the probability of the ion electron collisions in the ICR trap. This method has in fact been used to obtain improved ECD results: Tsybin, Y. O., Hxc3xa1kansson, P., Budnik, B. A., Haselmann, K. F., Kjeldsen, F., Gorshkov, M. and Zubarev, R. A.; xe2x80x9cImproved Low Energy Electron Injection Systems for High Rate Electron Capture Dissociation in Fourier Transform ion Cyclotron Resonance Mass Spectrometryxe2x80x9d Rapid Commun. Mass Spectrom. 2001, 15, 1840-1854. Also, the published International patent application WO 02/078048 A1 reports mass spectrometry methods using electron capture by ions.
Especially in the ion trap mass spectrometers, FT-ICR MS, RF ion traps, the interaction of stored ions with different partners (not only with photons but also with electrons but also with photons, etc.) can basically be studied. The infrared multiphoton dissociation described above is only one example of this. The dissociation of stored ions interacting with UV photons or with photons in the visible range is also being studied, as is the photo-induced excitation of ions, which does not lead to dissociation but to an increased reactivity with certain molecular reaction partners.
The designs of mass spectrometers, in particular ion traps, are usually enclosed and mostly do not allow a beam of the desired interaction partners enter the trap due to geometric reasons. For example, with RF traps (Paul traps), on the rotation axis of the trap, there is one aperture for the injection of externally generated ions and one aperture for their detection. If ions need to be generated within the trap volume by electron impact (internal ion generation), the external ion source generally has to be removed and an electron source has to be installed.
With the introduction of the new ECD fragmentation method, the supply of electrons into the ICR trap became important. ECD experiments can therefore now be carried out with thermal electrons. However, one of the two axial xe2x80x9centrancesxe2x80x9d into the ICR trap is already occupied by the xe2x80x9cnormalxe2x80x9d ion supply. A normal ion supply is defined as the supply of ions which have been generated in an ion source outside the trap. The other axial entrance is often used for infrared multiphoton dissociation experiments.
It is basically possible to place an electron source outside the axis and within the fringing fields of the superconductive magnet in order to generate an electron beam which travels along a field line near the axis of the trap. An example of this is described in: Schweikhard, L., Beiersdorfer, P., Bell, W., Dietrich, G., Krxc3xcckeberg, S., Lxc3xctzenkirken, K., Obst, B. and Ziegler, J. xe2x80x9cProduction and Investigation of Multiply Charged Metal Clusters in a Penning Trapxe2x80x9d Hyperfine Interactions 1996, 99, 97-104. Recently, however, shielded ICR magnets have been used almost exclusively so that the magnetic fringing fields are too small and thus not able to bundle the electron beam. Additionally, letting the electrons enter the area of high magnetic field is also made more difficult by the steep magnetic field gradients.
Since the external ion sources are steadily used in the FT-ICR mass spectrometry (the laser beam is introduced from the other side of the IDR trap and along its axis), both sides of the ICR trap in the magnetic field axis are occupied, and there is practically no possibility of installing an electron source for ECD fragmentation axially to the ion trap.
As the electron capture dissociation provides important results which are complementary to those obtained by infrared multi photon dissociation and collision induced dissociation, most users of FT ICR mass spectrometers aim to apply all three methods to substances being investigated. It would therefore be of great benefit to be able to switch between the fragmentation methods without having to go through time-consuming mechanical manipulations. It would also be desirable to use ECD and IRMPD on the same ions and, if possible, within the same experiment sequence. There would also be a major benefit in having a device and method for switching between IRMPD and ECD etc. rapidly and in an uncomplicated manner. Ideally, the insertion of an ion source into the path of the IR laser beam at the axis would be controlled by computer.
The use of shiftable or rotatable feedthroughs to move ion and electron sources represent a very limited solution. Furthermore, these methods are generally awkward and slow. Installing a shiftable or rotatable feedthrough is very unpractical, particularly in the ultra-high vacuum system used for Fourier transform mass spectrometry (operating in the range of 10xe2x88x9210 mbar). Furthermore, these devices are hardly suitable for carrying out experiments on a particular stored ensemble of ions. Aside from this, the methods used for switching over are time consuming and do not offer any possibility (particularly during routine operation) of performing electron and photon interaction studies using the same stored ions in the same sequence of experiments.
It is also worth mentioning another ion dissociation method which has recently been used to obtain information on structure, namely surface induced dissociation, SID. With this method, a prepared surface is required which is attached near to the inner surface of an ion trap such as an ICR trap. This surface is usually inserted into the vacuum system axial to the ICR trap. For this purpose, a surface probe is introduced through an ultrahigh vacuum lock system near the trap using a probe rod or is mounted directly at the trap itself. An article about SID in FT-ICR is: Zhong, W., Nikolaev, E., Futrell, J. H., and Wysocki, V. H. xe2x80x9cTandem Fourier Transform Mass Spectrometry Studies of Surface-Induced Dissociation of Benzene Monomer and Dimer Ions on a Self-Assembled Fluorinated Alkanethiolate Monolayer Surfacexe2x80x9d Anal Chem. 1997, 69, 2496-2503. Such a surface probe (similar to an electron source independent of the fact if it is inserted with a probe rod or is permanently attached) obstructs the path to the ICR trap and prevents a rapid switch, if for example, the ions stored in the ion trap need to be exposed to a laser beam.
Finally, the possibility of using fluorescence spectroscopy for the detection and analysis of stored groups of ions should also be mentioned. The following paper has recently been published on this topic: Wang, Y., Hendrickson, C. L. and Marshall, A. G. xe2x80x9cDirect Optical Spectroscopy of Gas-Phase Molecular Ions Trapped and Mass-Selected by Ion Cyclotron Resonance: Laser-induced Fluorescence Excitation Spectrum of Hexafluorobenzene (C6F6+), Chem. Phys. Lett, 2001, 334, 69-75. This method also requires unhindered optical access. However, the entrance on the axis is obstructed when an electron source has been installed there.
The present invention provides for the moving of an electron source to and from different positions in order to provide an electron beam or to clear the path for other beams as necessary. The idea of the invention is to build an electron source which can be moved between different positions making use of the Lorentz force. While the electron source is in a parking position, a beam such as a laser beam or an ion beam can be introduced into an ion trap without hindrance, or alternatively, optical observations of the stored ions can be performed. The Lorentz force, which moves the electron source into the operating position, can be produced by the operating current of a heated cathode, for example. The operating current is defined as the heating current of a filament or an indirectly heated electron source. The magnetic field can for example be the field which anyway exists in a Fourier transform ion cyclotron resonance mass spectrometer. However, in other types of mass spectrometers without magnetic field, the field can be produced just for moving the electron source.
In the following, the device and method used in the case of a directly heated thermionic cathode will be described first. The electrical current, typically one ampere, passes through a filament made of a metal such as tungsten or rhenium and heats up the filament. The electrons which escape by thermionic emission are extracted by applying an electrical voltage. If the filament (length L) is located in a magnetic field (flux density B) then, with a current I, a Lorentz force FL=ILxc3x97B where FL, L and B are vector parameters, and the force is FL=ILB sin(xcex1), where xcex1 is the angle between the conductor through which the current flows and the direction of the magnetic field line. Thus, no force is applied on conductors running parallel to the magnetic field. In conductors which are directed perpendicular to the magnetic field a force appears, which is perpendicular both to the conductor and the magnetic field. An example is the electron source in a Fourier transform ion cyclotron mass spectrometer FT ICR MS where a current of 2 A flows through the typically 0.5 cm long filament in a magnetic field of 7 Tesla. This produces a force of 0.07 Newtons, which corresponds approximately to the weight of a cubic centimeter of iron. With a rigidly mounted filament construction, the Lorentz force is taken up and compensated by the filament holder. However, if the filament is mounted on a movable frame, then it is possible for the Lorentz force to move the complete frame with the filament with current flowing through. The electron source can therefore be moved between different spatial positions.
A parking position and an operating position can for example be defined in such a way that if the filament heating current is switched on, the filament can be moved from the parking position to the operating position automatically. The operating position can be on the axis of the ICR trap in the vicinity of the trap. If the filament is in the parking position, then the electron source does not obstruct the axis of the instrument, so that, e.g., a laser beam can be coupled to the ICR trap or ions generated outside the trap can be transferred to the trap along the axis of the trap. It is therefore possible, if necessary, to move mobile electron sources on the axis of the trap in and out on both sides of an ICR trap. (Multiple mobile electron sources can also be attached on one side.)
There are different ways of returning the electron source from the operating position to the parking position. One possible arrangement is for the electron source to fall back to the parking position after switching off the heating current due to the force of gravity. It is also possible to attach a spring that pulls back the electron source to its parking position. Alternatively, reversing the filament current reverses the Lorentz force and it is also possible for this to be used to move back the electron source from operating position to its parking position. The same applies to reversing the direction of the magnetic field when using an electromagnet (see below). In order to define the operating and parking positions, end stops are made to limit the movement of the filament holding frame.
In general, multiple operating and parking positions can be used. Two filaments can, for example, be mounted as thermionic cathodes at opposite ends of an angled rotatable holder. Depending on the direction of the current, one or the other side is moved to the end stop at the operating position. The parking position is defined by the gravitational force that the center of gravity of the rotatable holder as it settles below the axis of rotation. In the parking position, the holder gives way for other applications such as the introduction of ion or laser beams into an ion trap or the optical observation of ions using fluorescent light etc. In this case, the two filaments can be connected in a way that they are electrically independent of each other or they can be connected in parallel. In the latter case, they can be of different length, width or thickness so that one can be used as a replacement for the other filament after it xe2x80x9cburns outxe2x80x9d.
In addition to the filaments heated by electrical current, there are other electron emission devices. These include indirectly heated cathodes and discharge tips. Microchannel plates can also be used as electron emitters. The use of a microchannel plate as an electron emitter is described in U.S. Pat. No. 6,239,549. These electron sources are not built as a simple loop of a conducting wire. Thus, it is advisable in this case to attach additional loops of conducting wire to the electron source in order to produce the required movement. When required, an electrical current is passed through these loops as described above for the heater filament.
Dispenser cathodes are an example of indirectly heated large-area cathodes. These can also be used as movable electron sources. In this case, they should be operated with a simple, i.e. non-bifilar heater solenoids. (Normally, these types of cathodes are equipped with bifilarly wound heater coils which prevent magnetic forces from acting on the cathode.) On the other hand, it is also possible to retain the bifilar heater winding and introduce an additional, independent winding in order to enable the required movement. On a microchannel plate which is used as electron emitter for example in the magnetic field of an FT ICR mass spectrometer, an extra winding can be attached in order to move it in the magnetic field using the Lorentz force.
The FT ICR MS provides the magnetic field automatically. However, movable electron sources can also be used in other mass spectrometers which do not have a magnetic field in the vicinity of the electron source. In this case, a permanent magnet or an electromagnet can be installed to provide the magnetic field required for moving the electron source.
Moving the electron source can be used to free the way into the ion trap for other particles such as ions or protons. But the electron source can also be moved in order to free the way for electrons, ions or protons which emerge from the ion trap and these can then be detected with the appropriate external detectors. In general, several electron sources with movable holders can be used either on one side or both sides of the ion trap.